Effects of subject-variability on nasally inhaled drug deposition, uptake, and clearance

Accurate and realistic predictions of the fate of nasally inhaled generic drugs provide new physical insight which can be of great importance to toxicologists, drug developers and federal regulators alike. To understand the dynamics of mucociliary clearance (MCC) and subsequent absorption of the dis...

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Published inJournal of aerosol science Vol. 165; p. 106021
Main Authors Chari, Sriram, Sridhar, Karthik, Kleinstreuer, Clement
Format Journal Article
LanguageEnglish
Published Elsevier Ltd 01.09.2022
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Online AccessGet full text
ISSN0021-8502
1879-1964
DOI10.1016/j.jaerosci.2022.106021

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Abstract Accurate and realistic predictions of the fate of nasally inhaled generic drugs provide new physical insight which can be of great importance to toxicologists, drug developers and federal regulators alike. To understand the dynamics of mucociliary clearance (MCC) and subsequent absorption of the dissolved drug by the nasal epithelium, it becomes necessary to model the air-particle-mucus dynamics accurately. The MCC process, including particle dissolution, transport and absorption for a 3-D representative nasal cavity, were established by Chari et al. (2021). In this study, the effects of inter-subject variability of three representative nasal cavities (subjects A, B, C) on deposition and subsequent uptake of the dissolved drug in the nasal epithelium are analyzed for three generic drugs: Mometasone furoate (MF), Flunisolide (FN), and Ribavirin (RB). The computational fluid-particle dynamics (CF-PD) results indicate that smaller sized particles (3 μm) deposit more in the ciliated portion of the nasal cavity where the columnar cells responsible for uptake are present. In contrast, larger particles (10 μm) tend to deposit in the unciliated anterior third of the nose. The epithelial uptake in case of subject A was considerably higher than that in subjects B and C because of the unique anatomical characteristics of subject A. Also, FN and RB were found to have a higher rate of uptake compared to MF due to their considerably higher partition coefficient. As a visualization tool, concentration contours are used to explain regional trends in cumulative drug uptake for all three cases. •The open-source CFD toolbox, OpenFOAM, has been employed for the development of the computer simulation model.•This study illustrates the effects of inter-subject variability on deposition, dissolution and uptake of 3 generic drugs in representative nasal cavity models.•Smaller particles, with their relatively large surface area, tend to dissolve quicker and are absorbed more rapidly than larger particles.•Particles deposited closer to the ciliated portion of the nasal cavity are more readily absorbed when compared to particles deposited closer to the unciliated nasal vestibule.
AbstractList Accurate and realistic predictions of the fate of nasally inhaled generic drugs provide new physical insight which can be of great importance to toxicologists, drug developers and federal regulators alike. To understand the dynamics of mucociliary clearance (MCC) and subsequent absorption of the dissolved drug by the nasal epithelium, it becomes necessary to model the air-particle-mucus dynamics accurately. The MCC process, including particle dissolution, transport and absorption for a 3-D representative nasal cavity, were established by Chari et al. (2021). In this study, the effects of inter-subject variability of three representative nasal cavities (subjects A, B, C) on deposition and subsequent uptake of the dissolved drug in the nasal epithelium are analyzed for three generic drugs: Mometasone furoate (MF), Flunisolide (FN), and Ribavirin (RB). The computational fluid-particle dynamics (CF-PD) results indicate that smaller sized particles (3 μm) deposit more in the ciliated portion of the nasal cavity where the columnar cells responsible for uptake are present. In contrast, larger particles (10 μm) tend to deposit in the unciliated anterior third of the nose. The epithelial uptake in case of subject A was considerably higher than that in subjects B and C because of the unique anatomical characteristics of subject A. Also, FN and RB were found to have a higher rate of uptake compared to MF due to their considerably higher partition coefficient. As a visualization tool, concentration contours are used to explain regional trends in cumulative drug uptake for all three cases. •The open-source CFD toolbox, OpenFOAM, has been employed for the development of the computer simulation model.•This study illustrates the effects of inter-subject variability on deposition, dissolution and uptake of 3 generic drugs in representative nasal cavity models.•Smaller particles, with their relatively large surface area, tend to dissolve quicker and are absorbed more rapidly than larger particles.•Particles deposited closer to the ciliated portion of the nasal cavity are more readily absorbed when compared to particles deposited closer to the unciliated nasal vestibule.
ArticleNumber 106021
Author Kleinstreuer, Clement
Chari, Sriram
Sridhar, Karthik
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Keywords Dissolution and absorption of three generic drugs
Nasal geometric variabilities
Mucus layer dynamics
CF-PD analysis With updated OpenFOAM solver
Mucociliary clearance
Inhaled drug-aerosol transport and uptake
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Snippet Accurate and realistic predictions of the fate of nasally inhaled generic drugs provide new physical insight which can be of great importance to toxicologists,...
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SubjectTerms CF-PD analysis With updated OpenFOAM solver
Dissolution and absorption of three generic drugs
Inhaled drug-aerosol transport and uptake
Mucociliary clearance
Mucus layer dynamics
Nasal geometric variabilities
Title Effects of subject-variability on nasally inhaled drug deposition, uptake, and clearance
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